Is ERMP1 p.Ser69Cys (c.206C>G) pathogenic?

ERMP1 p.Ser69Cys (c.206C>G) is classified Uncertain significance in ERMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1493); Ultra-rare (popmax 0.0451%, nfe).

How common is ERMP1 p.Ser69Cys (c.206C>G) in the general population?

ERMP1 p.Ser69Cys (c.206C>G) is ultra-rare (popmax 0.0451%, nfe) (gnomAD).

What do computational predictors say about ERMP1 p.Ser69Cys (c.206C>G)?

AlphaMissense predicts likely benign (score 0.1493) — an in-silico prediction, not a clinical call.

ERMP1 p.Ser69Cys

c.206C>G · rs747748510 · VCV2588294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1493 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1493	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -3.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.11, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 46 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0451% European (non-Finnish) · 512/1,134,208 alleles

Filtering AF 0.0419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0406%

Overall 0.0347% 521/1,503,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0451%	2,215
Remaining individualsnot grpmax-eligible	0.0103%	9,741
African / African-American	0.0029%	34,474
Admixed American	0.00211%	47,288

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERMP1
Protein: p.Ser69Cys
Coding: c.206C>G
MANE Select: NM_024896
dbSNP: rs747748510
Type: single nucleotide variant
Location: chr9:5832822 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.45

Full ERMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERMP1 c.1021+6T>C Likely benign ★★ same type
ERMP1 p.Gly809= Benign ★★ same type
ERMP1 p.Ser531= Benign ★★ same type
ERMP1 p.Val404= Benign ★★ same type
ERMP1 p.Ala109Gly Uncertain significance ★ ⚠ same type
ERMP1 p.Ala109Val Uncertain significance ★ ⚠ same type
ERMP1 p.Ala112Thr Uncertain significance ★ ⚠ same type
ERMP1 p.Ala196Asp Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ermp1-p-ser69cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown